LSD1失序区域的自抑制开关控制了增强器沉默的控制
Amanda L Waterbury1, Hui Si Kwok1, Ceejay Lee1
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Molecular cell
|June 13, 2024
概括
核心压缩器LSD1的内在无序区域 (IDR) 作为一个开关,防止转录因子 (TF) 的结合. 这种机制控制了基因抑制,对白血病细胞分化至关重要.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 基因法规 基因法规
背景情况:
- 转录因子 (TF) 和协同调节器利用内在无序区域 (IDR) 进行基因调节.
- IDRs促进多价值物相互作用,促进TFs和共同调节器之间形成蛋白质凝聚物.
研究的目的:
- 调查LSD1核心压缩体IDR在TF结合和基因抑制中的作用.
- 阐明LSD1 IDR调节活跃cis调节元件抑制的机制.
主要方法:
- -交换质谱 (HDX-MS) 用于分析IDR的结构动态.
- 研究了LSD1 IDR构成对TF凝结物形成的影响.
- 评估了LSD1在通过cis-regulatory元素抑制控制白血病分化中的作用.
主要成果:
- LSD1 IDR在开放和闭合的形状状态之间动态切换.
- LSD1 IDR的封闭状态抑制了其结构域与TF凝聚物的关联.
- 这种自身抑制机制调节了由LSD1和血液生成TFs结合的活性cis-regulatory元素的抑制.
结论:
- 无序的区域可以作为自我抑制的开关,不包括TF协会.
- IDRs和结构化区域之间的相互作用塑造了调节器-TF相互作用.
- 这种机制对于控制 cis 调节性场景和影响细胞命运至关重要,特别是在白血病分化中.
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